Continental and Antarctic Lichens: isolation, identification and molecular modeling of the depside tenuiorin from the Antarctic lichen Umbilicaria antarctica as tau protein inhibitor

Abstract

Alzheimer´s disease (AD) is the most common form of dementia involving Aβ and tau protein. So far, AD cure remains elusive, but considering that AD progresses throughout tau pathology, which turns tau protein an appropriate target, besides tau is also included in other neurodegenerative disorders named as tauopathies. Here, we have isolated seventeen compounds belonging to six lichens species. Due to scarce of spectroscopic data of the compound 5,7-dihydroxy-6-methylphthalide, we explained their structural elucidation based on NMR data. In this study, we show that only tenuiorin from Umbilicaria antarctica inhibited 50% of tau 4R at 100 µM. Then, we shown that molecular interactions of tenuiorin with the steric zipper model of the hexapeptide ³⁰⁶VQIVYK³¹¹ were studied by docking calculations and the results suggested that tenuiorin forms both hydrogen bonds with lysine and glutamine side chains and forms several hydrophobic interactions with valine and lysine from ³⁰⁶VQIVYK³¹¹ motif.

Keywords:

• Alzheimer´s disease
• Tau protein
• Lichens

Acknowledgements

This work was supported by the [Fondecyt Regular] under Grant [N° 1150745]; and [INACH] under Grant [RT 13-13 and MT 03-14].

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Fondecyt Regular (N° 1150745) and INACH (RT 13-13 and MT 03-14). Fondo Nacional de Desarrollo Científico and Tecnológico.